Nicotine reduces social dominance and neutralizes experience-dependent effects during social conflicts in zebrafish...

Nicotine, a psychoactive pollutant, binds to nicotinic acetylcholine receptors and disrupts the cholinergic modulation and reward systems of the brain, leading to attention deficit, memory loss, and addiction. However, whether nicotine affects social behaviors remains unknown. We assessed the effects of nicotine on the fighting behavior of zebrafish. Adult zebrafish treated with 5 μM nicotine were used in dyadic fighting tests with size-matched control siblings. The results indicate that nicotine treatment not only significantly reduced the likelihood of winning but also impaired the winner-loser effects (winner and loser fish did not show higher winning and losing tendencies in the second fight, respectively, after treatment.) Nicotine led to a considerable increase in c-fos-positive signals in the interpeduncular nucleus (IPN) of the brain, indicating that nicotine induces neural activity in the habenula (Hb)-IPN circuit. We used transgenic fish in which the Hb-IPN circuit was silenced to verify whether nicotine impaired the winner-loser effect through the Hb-IPN pathway. Nicotine-treated fish in which the medial part of the dorsal Hb was silenced did not have a higher winning rate, and nicotine-treated fish in which the lateral part of the dorsal Hb was silenced did not have a higher loss rate. This finding suggests that nicotine impairs the winner-loser effect by modulating the Hb-IPN circuit. Therefore, in these zebrafish, nicotine exposure impaired social dominance and neutralized experience-dependent effects in social conflicts, and it may thereby disturb the social hierarchy and population stability of such fish.